Uncover the immune biomarkers underlying hepatitis B e antigen (HBeAg) seroconversion: a need for more translational study.

The Hepatitis B e antigen (HBeAg) is a non-particulate secretory protein, which is not essential for viral assembly or replication but is important for the establishment of persistent infection in vivo. A recent study suggested that it down-regulates the innate immune response to infection and function as a T cell tolerogen [1]. For patients with chronic HBeAg positive chronic hepatitis B infection (CHB), HBeAg seroconversion, defined as loss of HBeAg with the appearance of anti-HBe, is often associated with clinical remission and a transition to inactive liver disease [2]. Accompanying HBeAg seroconversion, there is a reduction in liver fibrosis, a lower incidence of cirrhosis and hepatocellular carcinoma. HBeAg seroconversion, whether spontaneous or treatment-induced, is also associated with a higher probability of hepatitis B surface antigen (HBsAg) loss and seroconversion, which is considered to be a more permanent clinical remission of liver disease. Thus, the achievement and maintenance of HBeAg seroconversion, in association with polymerase chain reactionundetectable hepatitis B virus (HBV) DNA levels, are an important goal in the management of patients with HBeAg-positive CHB. Based on evidence demonstrating HBeAg seroconversion as an important hallmark event of a durable clinical remission of liver disease, major liver societies treatment guidelines have adopted HBeAg seroconversion with sustained suppression of HBV DNA as an end point for treatment in patients with HBeAg-positive CHB who do not have cirrhosis or decompensated liver disease. To date, there are seven registered treatments for CHB, two immunomodulatory agents – conventional interferon-a and pegylated interferon a2a – and five nucleos(t)ide analogues (NUCs) – lamivudine, adefovir dipivoxil, telbivudine, entecavir, and tenofovir dipropoxil. Among the various forms of treatment, one-year treatment with pegylated interferon a2a yielded the highest rate of HBeAg seroconversion (around 40%) and among them, one-tenth further benefit from HBsAg seroconversion. On the other hand, treatment with NUCs achieved a much lower rate